Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Buenos Aires, Argentina.
Microbiol Spectr. 2022 Aug 31;10(4):e0135722. doi: 10.1128/spectrum.01357-22. Epub 2022 Aug 8.
Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events ( = 22) and compared with those without adverse events ( = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4 and CD8 T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4 and CD8 T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.
皮炎是慢性恰加斯病患者接受苯唑硝唑治疗时最常见的不良反应，可能由 T 细胞介导。在接受苯唑硝唑治疗期间出现皮炎的感染了克氏锥虫的患者的循环和皮肤活检中，评估了一组代表不同 IV 型超敏反应的分子。通过流式细胞术珠分析和酶联免疫吸附试验捕获技术，测量了在接受苯唑硝唑治疗时出现皮肤不良反应的感染了克氏锥虫的患者（ = 22）和无不良反应的患者（ = 37）的血清细胞因子、趋化因子、促凋亡分子以及嗜酸性粒细胞和 T 细胞活化和迁移的介质水平。在有皮炎的患者中，IL-5、可溶性 Fas 细胞表面死亡受体配体 (FAS-L) 和干扰素 γ 诱导蛋白 (IP-10) 的血清水平在接受苯唑硝唑治疗后 7 至 30 天内显著增加，此后降低，但在无皮炎的患者中则没有。有皮炎的患者的循环嗜酸性粒细胞趋化因子水平较低。皮肤活检中出现两种模式：辅助性 T 细胞 1/细胞毒性 T 细胞和辅助性 T 细胞 2/细胞毒性 T 细胞，伴有 CD4 和 CD8 T 细胞。在接受苯唑硝唑治疗期间发生皮炎的患者中，出现了低密度脂蛋白 (LDL)、谷草转氨酶 (GOT)、尿毒症和 T 细胞活化等危险因素。这些结果支持对苯唑硝唑的迟发型超敏反应，涉及 CD4 和 CD8 T 细胞和嗜酸性粒细胞，以及混合细胞因子谱。这项研究为更好地管理苯唑硝唑的药物不良反应提供了新的见解。本研究确定了苯唑硝唑不良反应发生的危险因素，并确定了一组分子来监测这些反应的出现。这些知识可能会提高苯唑硝唑给药的安全性。
